Gancao Xiexin Decoction ameliorates recurrent oral ulcers via TNF-α pathway-mediated suppression of oxidative stress

Recurrent oral ulcer (ROU), a chronic inflammatory disorder of the oral mucosa characterized by recurrent painful ulcerations, significantly compromises patients' dietary intake, speech, and quality of life. While its precise etiology remains elusive, the dynamic interplay between oxidative stress and inflammatory responses has emerged as a pivotal mechanism underlying ROU pathogenesis. Gancao Xiexin Decoction (GCXXD), a traditional Chinese formulation with demonstrated anti-inflammatory and antioxidant properties, has shown clinical efficacy in gastrointestinal disorders such as inflammatory bowel disease, yet its pharmacological mechanisms require systematic exploration. This study integrates transcriptomic profiling and network pharmacology to elucidate GCXXD's therapeutic mechanisms against ROU. Through mining traditional Chinese medicine component databases and transcriptomic datasets, we identified 10 bioactive constituents of GCXXD, with wogonin, luteolin, liquiritin, and berberine exhibiting prominent anti-inflammatory/antioxidant activities as potential key mediators. Functional enrichment analyses (gene ontology/Kyoto encyclopedia of genes and genomes) revealed critical involvement of tumor necrosis factor and NF-κB signaling pathways in ROU progression. Mechanistically, GCXXD likely ameliorates ROU by modulating immunoinflammatory factors (e.g., tumor necrosis factor-α) through these core components, thereby suppressing oxidative-inflammatory cascades. Our findings provide novel insights into the molecular basis of GCXXD's anti-ROU effects and advance the application of traditional Chinese medicine in mucosal immunity regulation.